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Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains

The bacterial species Staphylococcus aureus presents a variety of resistance mechanisms, among which the expression of β-lactamases and efflux pumps stand out for providing a significant degree of resistance to clinically relevant antibiotics. The 1,8-naphthyridines are nitrogen heterocycles with a...

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Detalles Bibliográficos
Autores principales: Oliveira-Tintino, Cícera Datiane de Morais, Tintino, Saulo Relison, Justino de Araújo, Ana Carolina, dos Santos Barbosa, Cristina Rodrigues, Ramos Freitas, Priscilla, de Araújo Neto, José Bezerra, Begnini, Iêda Maria, Rebelo, Ricardo Andrade, da Silva, Luiz Everson, Mireski, Sandro Lucio, Nasato, Michele Caroline, Krautler, Maria Isabel Lacowicz, Barreto, Humberto Medeiros, Ribeiro-Filho, Jaime, de Menezes, Irwin Rose Alencar, Coutinho, Henrique Douglas Melo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961278/
https://www.ncbi.nlm.nih.gov/pubmed/36838807
http://dx.doi.org/10.3390/molecules28041819
Descripción
Sumario:The bacterial species Staphylococcus aureus presents a variety of resistance mechanisms, among which the expression of β-lactamases and efflux pumps stand out for providing a significant degree of resistance to clinically relevant antibiotics. The 1,8-naphthyridines are nitrogen heterocycles with a broad spectrum of biological activities and, as such, are promising research targets. However, the potential roles of these compounds on bacterial resistance management remain to be better investigated. Therefore, the present study evaluated the antibacterial activity of 1,8-naphthyridine sulfonamides, addressing their ability to act as inhibitors of β-lactamases and efflux pump (QacA/B and QacC) against the strains SA-K4414 and SA-K4100 of S. aureus. All substances were prepared at an initial concentration of 1024 μg/mL, and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. Subsequently, their effects on β-lactamase- and efflux pump-mediated antibiotic resistance was evaluated from the reduction of the MIC of ethidium bromide (EtBr) and β-lactam antibiotics, respectively. The 1,8-naphthyridines did not present direct antibacterial activity against the strains SA-K4414 and SA-K4100 of S. aureus. On the other hand, when associated with antibiotics against both strains, the compounds reduced the MIC of EtBr and β-lactam antibiotics, suggesting that they may act by inhibiting β-lactamases and efflux pumps such as QacC and QacA/B. However, further research is required to elucidate the molecular mechanisms underlying these observed effects.